The retinoic acid-binding protein (RABP), that may mediate the biological function of retinoic acid in epithelial differentiation and in the control of tumorigenesis, has been detected in most of the retinoid responsive tissues of rat, mouse and chick embryo. Analysis for RABP in four experimental murine colon tumors revealed the presence of this protein in two metastatic colon tumors and its virtual absence in the other two non-metastatic colon tumors. After s.c. implantation of a metastatic colon tumor (#26) into mice, RABP could be traced in the lungs on the 5th day due to pulmonary metastasis, whereas in the normal mouse lungs the protein was below the limits of detection. In primary cultures of colon tumor 26, the lower limit for detection of RABP corresponded to 0.1 mg extractable protein that could be derived from 3 mg tumor and is equivalent to 2.5 times 10 to the 4th power cells in primary culture. Out of 27 human colon tumor specimens and related materials examined for RABP, the binding protein has been detected in 90% of the human colon, secum and colorectal tumors. Further evaluation of RABP levels in human specimens and comparison with pathological findings is needed before a general correlation can be made between malignant tumorigenesis and the appearance of RABP.